Phase II Study of S-1, a Novel Oral Derivative of 5-Fluorouracil, in Advanced Gastric Cancer

Abstract

Purpose: To assess the efficacy and safety of S-1, a novel oral fluoropyrimidine derivative, we conducted a multicenter late phase II study in patients with advanced gastric cancer. Patients and Methods: Fifty-one patients who had received no previous chemotherapy were enrolled. Fifty patients were eligible for efficacy and safety analyses. The overall response was evaluated for the 43 patients who had metastatic lesions. S-1 was administered orally after breakfast and dinner for 28 days, followed by a 14-day break. The dosages were assigned according to the patients’ body surface area (BSA): BSA <1.25 m², 40 mg; 1.25–1.5 m², 50 mg, and BSA ≥1.5 m², 60 mg, twice daily. Results: The overall response to treatment was evaluated as partial response in 19 of the 43 patients (44%; 95% confidence interval 30–59%). The median survival time in all patients was 207 days with 1- and 2-year survival rates of 36.0 and 14.0%, respectively. Grade 3 adverse reactions included decreased hemoglobin values in 2 patients, leukopenia, neutropenia and diarrhea in 1 patient each. No other grade 4 or unexpected adverse reactions were seen. Conclusions: S-1 is effective against advanced gastric cancer. This oral treatment is suitable for outpatients because of its mild toxicity. Further therapeutic benefits are likely to be obtained by combining S-1 with other chemotherapeutic agents.

Phase I/II study of S-1 combined with paclitaxel in patients with unresectable and/or recurrent advanced gastric cancer

“…The MST in our study was longer than that in previous phase II studies of S-1 as a single agent (207 -250 days) (Sakata et al, 1998;Koizumi et al, 2000). Our response rate is equivalent to that reported for TS-1/cisplatin therapy (Koizumi et al, 2003).…”

“…Two late phase II trials of S-1 therapy in Japanese patients with advanced gastric cancer have reported a high overall response rate of 44 -49% and an MST of 7 -8 months (Sakata et al, 1998;Koizumi et al, 2000). These findings suggest that S-1 is one of the most effective currently available antitumour agents for gastric cancer.…”

“…In one early phase II clinical trial of S-1, the response rate was 53.6% (15 out of 28), and the median survival period was 298 days in Japanese patients with advanced gastric cancer (Horikoshi et al, 1996). Two late phase II studies of S-1 in advanced gastric cancer, which used similar treatment regimens, demonstrated high response rates of 49 and 44%, respectively (Sakata et al, 1998;Koizumi et al, 2000). These results suggested that S-1 is likely to become a key drug for the management of advanced gastric cancer.…”

“…A number of studies have reported that S-1 monotherapy is effective against gastric cancer, with response rates ranging from 26 to 53% (Horikoshi et al, 1996;Sakata et al, 1998;Koizumi et al, 2000;Chollet et al, 2003). The toxicity profile of S-1 in European studies apparently differs from that in Japanese studies, with more diarrhoea and hand-foot syndrome and less myelotoxicity (Chollet et al, 2003).…”

EORTC Early Clinical Studies Group early phase II trial of S-1 in patients with advanced or metastatic colorectal cancer

“…Phase II studies showed activity of S-1 in breast cancer, head and neck cancer, colorectal, gastric cancer and nonsmall-cell lung cancer, with mild to moderate toxicity (Inuyama et al, 1998;Sakata et al, 1998;Sugimachi et al, 1999;Taguchi et al, 1998;Koizumi et al, 2000;Kawahara et al, 2001;Ohtsu et al, 2000). S-1 is in Japan already widely used in patients with gastric cancer and head and neck cancer.…”